Mentorship in the Endocrinology of Sleep

申请K24职业生涯中期研究人员奖的首要目标是以患者为中心的研究 是培养有前途的初级调查人员，从事与以下方面有关的以病人为导向的前沿研究 睡眠生物学影响心脏代谢健康。它利用已建立的网络和 最近更新了加州大学洛杉矶分校的CTSI，其中包括一个非常成功的KL2项目。刘博士领导了一项具有竞争力的- 悉尼大学睡眠生物学内分泌和心脏代谢项目的资助，自2012年以来， 他在洛杉矶领导了一个类似的跨学科研究项目，得到了为期5年的NHLBI R01的支持 “睡眠受限的荷尔蒙机制”目前已进入第三个年头。在他10年的指导生涯中， 他已经培训了16个人：10个人留在学术医学领域，另外2个人在行业相关患者方面 有针对性的研究。在他的监督下，他的三名实习生获得了美国主要年轻调查员奖。他 继续支持、指导和出版前学员，通常是在他们离开他的实验室很久之后。 睡眠障碍会导致胰岛素抵抗，促进糟糕的食物选择，并在节食时减少脂肪损失， 从而降低了标准减肥计划的有效性。然而，心脏新陈代谢 睡眠障碍的后果没有得到社区的很好认识，也没有证据证明 由于心脏代谢健康的原因，社区睡眠模式正在发生广泛的变化。显出 睡眠限制导致心脏代谢不良的机制，特别是在老年人中 根据性别，是提供这些数据的关键步骤。刘博士的目标是指导下一代干部 独立临床科学家专注于将睡眠与饮食和锻炼放在一起，作为健康生活方式的一部分。 通过了解荷尔蒙机制和睡眠中断、不足或错位的后果。 本申请中提出的工作实现了这些目标。目标1将揭示下丘脑-垂体-肾上腺 和下丘脑-垂体-性腺机制，导致睡眠时睾酮-皮质醇失衡 仅限老年男性和女性(每组20人)。在此过程中，学员将学习内分泌生理学和 时间生物学研究设计、IRB流程、招聘技能和实践研究管理。目标2将 确定这些机制中的性别差异，受训者将学习统计方法和摘要/陈述/ 手稿准备工作。目标3要求受训者发现睡眠限制引起的新机制 胰岛素抵抗，改变食欲或食物摄入量。某些炎症介质、激素或因子 可以研究与种族或年龄有关的问题。AIM 3满足了对学员有第二个孩子的更广泛期望 项目完成速度更快，更具探索性，并受到他们的兴趣和可用资源的驱动，以 发展一条与导师的研究相辅相成、相互独立的研究路线。这些加在一起， 实验将产生关于睡眠和荷尔蒙心脏代谢和睡眠之间关系的新知识 生殖健康，提供广泛的培训机会，并产生未来的R和K提案。

The overarching goal of this application for a K24 Midcareer Investigator Award in Patient-Oriented Research is to foster training of promising junior investigators in cutting edge patient-oriented research related to how sleep biology influences cardiometabolic health. It capitalizes on the established network and resources of the recently renewed UCLA CTSI that includes a highly successful KL2 program. Dr. Liu led a competitively- funded Endocrine and Cardiometabolic Program in Sleep Biology at the University of Sydney, and since 2012, he has led a similar interdisciplinary research program in Los Angeles supported by a 5 year NHLBI R01 “Hormonal mechanisms of sleep restriction” that is currently in its 3rd year. During his 10 years of mentoring, he has trained 16 individuals: 10 remaining in academic medicine and 2 others in industry-related patient orientated research. Three of his trainees won major US young investigator awards under his supervision. He continues to support, mentor, and publish with former trainees, often long after they left his laboratory. Disturbed sleep causes insulin resistance, promotes poor food choices, and curtails fat loss while dieting, thereby reducing the effectiveness of standard weight loss programs. However, the cardiometabolic consequences of disturbed sleep are not well recognized by the community, and the evidential bases to justify widespread changes to community sleeping patterns for cardiometabolic health reasons are evolving. Showing the mechanisms by which sleep restriction leads to cardiometabolic ill-health, particularly in older adults according to sex, are critical steps in providing these data. Dr. Liu's goal is to mentor the next cadre of independent clinical scientists focused on placing sleep alongside diet and exercise as part of healthy lifestyle, by understanding hormonal mechanisms and consequences of disrupted, inadequate or misaligned sleep. The work proposed in this application fulfill these goals. Aim 1 will reveal the hypothalmo-pituitary-adrenal and hypothalamo-pituitary-gonadal mechanisms that cause testosterone-cortisol imbalance when sleep is restricted in older men and women (20 in each group). In doing so, trainees will learn endocrine physiology and chronobiological study design, IRB processes, recruitment skills, and hands-on study management. Aim 2 will identify sex differences in these mechanisms, trainees will learn statistical methods and abstract/presentation/ manuscript preparation. Aim 3 requires trainees to discover new mechanisms by which sleep restriction causes insulin resistance and alters appetite or food intake. Certain inflammatory mediators, hormones, or factors related to ethnicity or age could be studied. Aim 3 fulfils broader expectations for trainees to have a second project that is faster to accomplish, more exploratory, and driven by their interests and available resources, to develop a line of research that complements and is separate from that of the mentors. Taken together, these experiments will generate new knowledge of the relationship between sleep and hormonal cardiometabolic and reproductive health, provide wide-ranging training opportunities, and generate future R and K proposals.